Clinical phenotyping in patients with anti-synthetase antibodies using cluster analysis.

Objectives: To characterize clinically distinct subgroups among unselected patients with anti-synthetase antibodies using cluster analysis. Methods: This study evaluated patients with anti-synthetase antibodies registered to two independent cohorts; 106 consecutive patients from a prospective, single-centre cohort of the Scleroderma/Myositis Centre of Excellence (SMCE) were used as a derivation cohort and 125 patients from the Multicentre Retrospective Cohort of Japanese Patients with Myositis-Associated Interstitial Lung Disease (JAMI) were used as a validation cohort. Anti-synthetase antibodies were identified by RNA immunoprecipitation. A multiple correspondence analysis followed by hierarchical clustering was performed to aggregate the patients into homogeneous subgroups. Subsequently, a simple-to-use classification tree was generated using classification and regression tree analysis. Results: Three clusters were identified in the SMCE cohort: cluster 1 (n = 48), the interstitial pneumonia with autoimmune features/amyopathic dermatomyositis cluster, associated with older age at diagnosis and a higher frequency of malignancy; cluster 2 (n = 46), the DM cluster, corresponded to a younger age at diagnosis with a higher prevalence of myositis, arthritis, DM pathognomonic rashes, mechanic's hands and fever; and cluster 3 (n = 12), the SSc cluster, characterized by chronic interstitial lung disease. There was no significant difference in overall survival or progression-free survival between the clusters. A simple classification tree using myositis and RP was created in the SMCE cohort. Clusters 1 and 2 were successfully reproduced and the classification tree demonstrated favourable performance in the JAMI cohort. Conclusion: Patients with anti-synthetase antibodies were classified into three distinct phenotypes, indicating substantial heterogeneity within this patient group.

Simultaneous boost radiotherapy versus conventional dose radiotherapy for patients with newly diagnosed glioblastoma: a multi-institutional analysis.

We compared survival outcomes of high-dose concomitant boost radiotherapy (HDCBRT) and conventional dose radiotherapy (CRT) for newly diagnosed glioblastoma (GB). Patients treated with intensity-modulated radiation therapy for newly diagnosed GB were included. In HDCBRT, specific targets received 69, 60, and 51 Gy in 30 fractions, while 60 Gy in 30 fractions was administered with a standard radiotherapy method in CRT. Overall survival (OS) and progression-free survival (PFS) were compared using the Log-rank test, followed by multivariate Cox analysis. The inverse probability of treatment weighting (IPTW) method was also applied to each analysis. Among 102 eligible patients, 45 received HDCBRT and 57 received CRT. With a median follow-up of 16 months, the median survival times of OS and PFS were 21 and 9 months, respectively. No significant differences were observed in OS or PFS in the Kaplan-Meier analyses. In the multivariate analysis, HDCBRT correlated with improved OS (hazard ratio, 0.49; 95% confidence interval, 0.27-0.90; P = 0.021), and this result remained consistent after IPTW adjustments (P = 0.028). Conversely, dose suppression due to the proximity of normal tissues and IMRT field correlated with worse OS and PFS (P = 0.008 and 0.049, respectively). A prospective study with a stricter protocol is warranted to validate the efficacy of HDCBRT for GB.

The Role of Environmental Factors in the Development of Idiopathic Inflammatory Myopathies: a Narrative Review.

PURPOSE OF REVIEW: This review aims to evaluate recent findings on the role of environmental factors in the development and clinical presentation of idiopathic inflammatory myopathies (IIMs). RECENT FINDINGS: A targeted literature review was conducted to identify reports relevant to the association between environmental factors and IIMs published over the past three years. There has been an increasing number of publications dealing with the association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination with the development of IIMs, highlighting the significant role of the antiviral immune response in the pathogenesis of the disease. Traditional environmental factors associated with the pathogenic process of IIM subclassifications included drugs such as statins and immune checkpoint inhibitors, ultraviolet radiation, smoking, air pollutants, and vitamin D deficiency. Correlations of seasonality and residence with the onset of certain IIM subtypes suggest a potential role of environmental triggers in the pathogenic process. An interplay between genetic predisposition and various environmental factors might contribute to the development of IIMs as well as the heterogeneous clinical and serological presentation of IIMs. The growing evidence on the role of environmental factors in the development of IIMs provides important clues to elucidate the pathophysiology of these disease entities. The mechanisms underlying the interactions between genetic predisposition and environmental factors should be investigated in the future.

Clinical Outcomes of Radiation Therapy for Angiosarcoma of the Scalp and Face: A Multi-Institutional Observational Study.

Angiosarcoma of the scalp and face (ASF) is a rare, aggressive tumor often treated with multimodal therapy, including radiation therapy (RT). This study assessed RT outcomes for ASF and identified prognostic factors. Data from 68 non-metastatic ASF patients undergoing RT with or without other therapies were analyzed. Median radiation dose was 66 Gy in 33 fractions (interquartile range (IQR) 60-70 Gy in 28-35 fractions). Local control (LC), progression-free survival (PFS), and overall survival (OS) rates were calculated using Kaplan-Meier analysis. Multivariate analyses and adverse event evaluation were conducted. Median patient age was 75 years (IQR 71-80 years), with a median follow-up of 17 months (IQR 11-42 months). One-/three-year LC rates were 57/37%, PFS rates were 44/22%, and OS rates were 81/44%. Multivariate analyses showed that an equivalent dose in a 2 Gy fraction (EQD2) >66 Gy correlated with improved LC (HR 2.35, 95% CI 1.03-5.32, p = 0.041). Combining chemotherapy (HR 2.43, 95% CI 1.08-5.46, p = 0.032) or surgery (HR 2.41, 95% CI 1.03-5.59, p = 0.041) improved PFS. No factors influenced OS. Late grade 3+ toxicities occurred in 1%, with one patient developing a grade 4 skin ulcer. These findings suggest that EQD2 > 66 Gy and combining chemotherapy or surgery can enhance LC or PFS in ASF. Further prospective studies are needed to determine the optimal treatment strategy for this rare malignancy, particularly in elderly patients.

Elucidation of Late-Stage Biosynthesis of Phomoidride: Proposal of Cyclization Mechanism Affording Characteristic Nine-Membered Ring of Fungal Dimeric Anhydride.

Antihypercholesterolemic agent phomoidride (PMD) B has a highly elaborated bicyclo[4.3.1]deca-1,6-diene core scaffold derived from dimeric anhydride with a nine-membered ring. This report elucidated the late stage transformation from an anhydride monomer to PMD B through the heterologous expression of three enzyme genes, TstC, TstK, and TstE. Additional in vitro studies of TstK and TstE provided evidence on the formation of PMD via dimerization, three-step oxidation, and unusual methylation-triggered bicyclic ketal formation. Elucidation of the function of cyclase TstC prompts us to examine the cyclization mechanism of TstC by using a computational approach. Computational analytical data on PMD and structurally related glaucanic acid indicated that the initial decarboxylation of monomer results in enolate and subsequent double Michael reactions of another monomer, followed by an optional aldol reaction proceeding in an endo-selective manner to give cycloadducts, supporting the fact that the starting orientation of two monomers is directly transferred to the product configurations.

c-kit inhibitor masitinib induces reactive oxygen species-dependent apoptosis in c-kit-negative HepG2 cells.

Tumor-specific growth signal inhibition is a major anticancer strategy. Receptor tyrosine kinases (RTKs) are the most upstream receptors for growth signaling in cancer. Therefore, inhibition of RTKs has been proposed as an efficient therapeutic target. Masitinib, a c-kit inhibitor of the c-kit RTK, was developed to treat mastocytoma in dogs. In humans, however, the antitumor efficacy of masitinib was found to be attenuated against tumor cells with mutations of the c-kit gene. Here, we report that masitinib induced cell death via the intrinsic apoptotic pathway in HepG2, a c-kit-negative hepatocellular carcinoma cell line. In masitinib-treated HepG2 cells, increases in intracellular reactive oxygen species levels, loss of mitochondrial membrane potential, and cleavage of caspase-9 were observed, activating the intrinsic apoptotic pathway. Moreover, the cytotoxicity of masitinib to HepG2 cells was suppressed by treatment with the antioxidant N-acetyl-L-cysteine or a c-Jun N-terminal kinase/stress-activated protein kinase (JNKs) inhibitor. Thus, we demonstrated that the anticancer effects of masitinib are not due to its targeting c-kit, but rather to its targeting the redox balance via the JNK pathway in HepG2 cells. These results suggest that masitinib has the potential to provide a robust antitumor effect in tumor lesions and could also be applied to a broad range of other anticancer therapies.

Bronchogenic cyst with atypical imaging findings and repeated ruptures in a short period of time: A case report.

Bronchogenic cysts are the most common primary cysts of the mediastinum. Although most are asymptomatic, some bronchogenic cysts cause symptoms such as chest pain and dyspnea. Here, we report a case of bronchogenic cyst that ruptured twice in a short period of time in a patient who presented with sudden back pain. The lesion was apparent on computed tomography (CT) as a mass lesion with heterogeneous and high attenuation in the posterior mediastinal region. CT-guided puncture performed for diagnostic purposes revealed the contents as bloody fluid. The patient suffered chest pain approximately 3 months after the first presentation, and re-growth and re-rupture of the mass was suspected. The lesion was surgically resected and pathologically diagnosed as a bronchogenic cyst. Spontaneous rupture is a very rare complication of bronchogenic cyst, usually into the trachea, pleural cavity, or pericardial cavity. However, there are no reports of multiple ruptures. This case highlights the importance of recognizing the atypical imaging findings of bronchogenic cyst and the rare complication of rupture.

The "Ant-farm"-like Appearance of Restricted Lower Limb Vasculitis on Fluorodeoxyglucose-positron Emission Tomography.

Restricted lower limb vasculitis is a type of localized muscle vasculitis limited to the lower limbs. The usefulness of fluorodeoxyglucose-positron emission tomography (FDG-PET) for the diagnosis of this entity has not yet been reported. We herein report three patients with a fever and persistent lower limb pain. FDG-PET revealed linear and patchy FDG uptakes in their lower limbs. Combined with magnetic resonance imaging and histological findings, they were diagnosed with lower limb vasculitis. Linear and patchy FDG uptakes are considered to reflect the presence of muscle vasculitis. The characteristic "ant-farm"-like FDG-PET images can be a diagnostic clue for the currently overlooked vasculitis.

Visual Summary Identification From Scientific Publications via Self-Supervised Learning.

The exponential growth of scientific literature yields the need to support users to both effectively and efficiently analyze and understand the some body of research work. This exploratory process can be facilitated by providing graphical abstracts-a visual summary of a scientific publication. Accordingly, previous work recently presented an initial study on automatic identification of a central figure in a scientific publication, to be used as the publication's visual summary. This study, however, have been limited only to a single (biomedical) domain. This is primarily because the current state-of-the-art relies on supervised machine learning, typically relying on the existence of large amounts of labeled data: the only existing annotated data set until now covered only the biomedical publications. In this work, we build a novel benchmark data set for visual summary identification from scientific publications, which consists of papers presented at conferences from several areas of computer science. We couple this contribution with a new self-supervised learning approach to learn a heuristic matching of in-text references to figures with figure captions. Our self-supervised pre-training, executed on a large unlabeled collection of publications, attenuates the need for large annotated data sets for visual summary identification and facilitates domain transfer for this task. We evaluate our self-supervised pretraining for visual summary identification on both the existing biomedical and our newly presented computer science data set. The experimental results suggest that the proposed method is able to outperform the previous state-of-the-art without any task-specific annotations.

Barium-induced pneumatosis intestinalis in a patient with anti-synthetase syndrome.

Pneumatosis intestinalis is defined as the presence of gas in the bowel wall. The combination of the two risks, pre-existing connective tissue diseases and barium contrast examination, may trigger pneumatosis intestinalis, albeit at a low incidence. Clinicians should be aware of the condition for proper differential diagnosis.

Purple urine bags reflecting an aging society.

The purple urine bag syndrome is an underrecognized but quite common condition, resulting in marked discoloration of the urine bag system due to bacterial metabolism. This syndrome is associated with advanced age and bedridden persons.

Gait Phase Detection Based on Muscle Deformation with Static Standing-Based Calibration.

Gait phase detection, which detects foot-contact and foot-off states during walking, is important for various applications, such as synchronous robotic assistance and health monitoring. Gait phase detection systems have been proposed with various wearable devices, sensing inertial, electromyography, or force myography information. In this paper, we present a novel gait phase detection system with static standing-based calibration using muscle deformation information. The gait phase detection algorithm can be calibrated within a short time using muscle deformation data by standing in several postures; it is not necessary to collect data while walking for calibration. A logistic regression algorithm is used as the machine learning algorithm, and the probability output is adjusted based on the angular velocity of the sensor. An experiment is performed with 10 subjects, and the detection accuracy of foot-contact and foot-off states is evaluated using video data for each subject. The median accuracy is approximately 90% during walking based on calibration for 60 s, which shows the feasibility of the static standing-based calibration method using muscle deformation information for foot-contact and foot-off state detection.

Granulocyte-Colony Stimulating Factor-Induced Vasculitis Successfully Treated With Short-Term Corticosteroid Therapy: A Case Report.

Granulocyte-colony stimulating factor (G-CSF) is widely used for preventing neutropenia, and large vessel vasculitis has been recognized as one of its severe adverse events. We report a case of diffuse large B-cell lymphoma in a 78-year-old woman in whom fever and right cervical pain developed after administration of filgrastim. Computed tomography and cervical artery ultrasound imaging revealed wall thickening in the right common carotid artery. We diagnosed her with G-CSF-induced vasculitis and administered prednisolone of 50 mg/day (1 mg/kg/day) to her. Her symptoms disappeared in a few days, and prednisolone was discontinued six weeks after initiation. G-CSF-induced vasculitis may be improved with short-term high-dose corticosteroids with rapid tapering.

Provisional seven-item criteria for the diagnosis of polyarteritis nodosa.

Polyarteritis nodosa (PAN) is a potentially life-threatening systemic vasculitis, which predominantly involves medium arteries. However, it may be difficult to diagnose PAN in its early stage. The aim of our study was to investigate the sensitivity and specificity of the American College of Rheumatology (ACR) and the Japanese Ministry of Health, Labour and Welfare (MHLW) criteria for the diagnosis of PAN in a single-centre retrospective cohort in Japan and to develop simplified criteria with favourable diagnostic performance. All patients with "PAN" or "suspicion of PAN," as indicated on insurance forms, were included. The patient population was classified into PAN and non-PAN groups based on a retrospective chart review. The sensitivity and specificity of the ACR and MHLW criteria were calculated. Items that favourably discriminated the PAN group from the non-PAN group were determined and used as items for our provisional criteria. Thirteen cases of PAN and 24 cases without PAN were included in this study. The sensitivities of the ACR and MHLW criteria were 61.5% (8/13) and 30.8% (4/13), respectively, whereas the specificities were 79.2% (19/24) and 87.5% (21/24), respectively. We developed provisional criteria consisting of seven items, and found that a cut-off of ≥ 4 items had a sensitivity of 92.3% (12/13) and specificity of 91.7% (22/24) (p < 0.000001). The provisional seven-item criteria, developed in our real-world cohort of patients suspected of having PAN, had a high sensitivity and specificity and may be useful in the diagnosis of PAN, although it should be validated in additional patient populations.

Effect of chum salmon egg lectin on tight junctions in Caco-2 cell monolayers.

The effect of a chum salmon egg lectin (CSL3) on tight junction (TJ) of Caco-2 cell monolayers was investigated. The lectin opened TJ as indicated by the decrease of the transepithelial electrical resistance (TER) value and the increase of the permeation of lucifer yellow, which is transported via the TJ-mediated paracellular pathway. The effects of CSL3 were inhibited by the addition of 10 mM L-rhamnose or D-galactose which were specific sugars for CSL3. The lectin increased the intracellular Ca2+ of Caco-2 cell monolayers, that could be inhibited by the addition of L-rhamnose. The fluorescence immunostaining of ß-actin in Caco-2 cell monolayers revealed that the cytoskeleton was changed by the CSL3 treatment, suggesting that CSL3 depolymerized ß-actin to cause reversible TJ structural and functional disruption. Although Japanese jack bean lectin and wheat germ lectin showed similar effects in the decrease of the TER values and the increase of the intracellular Ca2+, they could not be inhibited by the same concentrations of simple sugars, such as D-glucose and N-acetyl-D-glucosamine.